The basic objective of this project is to determine the mechanism for regulation of total CoA levels in rat heart and liver and the mechanism for storage of ingested pantothenate and mobilization of storage pools. The project includes determining whether fluctuations of CoA in the liver, heart, or adrenal arising from an altered hormonal status (such as diabetes) or resulting from an altered dietary intake can impair or modify the functioning of these tissues. Measurements have been made of differences in the total CoA, pantothenate and p-pantetheine concentrations in the liver and hearts of alloxan-diabetic versus control rats, and of rats on a fasting-refeeding cycle, which give evidence for a hormonally-directed regulation of total CoA and intermediates on the biosynthetic pathway after 14C-pantothenate injection into the bloodstream are being compared in mitochondria versus freeze-clamped tissues, after force-feeding glucose and after insulin injection into a diabetic animal in order to determine the regulatory steps. A study is also being made of metabolic pathways and tissues affected by changes in CoA concentrations and by the dietary intake of pantothenate.